We have recently reported the isolation and partial characterization of a new plasma sialoglycoprotein with a molecular weight of 120 kDa (sgp 120). This protein has a number a properties similar to that of the second component of human complement (C2) and they are coisolated on C4b- Sepharose; the following differences have been noted. Sgp 120 is present in plasma at 15 x the concentration C2. These proteins do not cross immunoprecipitate with polyclonal antisera. They are activated and cleaved by distinct mediator pathways: sgp 120 by the contact-activation system (CAS) and C2 by the classical complement pathway (CCP). The proteins have unique N-terminal amino acid sequences and a C-terminal stretch of 50 residues within sgp 120 as determined by cDNA cloning and sequencing is unrecognized in any of 6000 screened sequences including C2, kallikrein and HMW kininogen. We have developed new methodology to prepare sgp 120. Sgp 120 cleavage was shown to be mediated by kallikrein in the contact-activation system resulting in the generation of distinct cleavage fragments. Initial proteolysis produces cleavage at 85 kDa from the N-terminal producing a 35 kDa fragment. Subsequent cleavage of the 85 kDa fragment at 60 kDa from the N-terminal produces a 25 kDa fragment. The ordering of the peptides was deduced from the N-terminal amino acid analyses of the respective components. We have shown that sgp 120 is a sialoglycoprotein containing about 6% sialic acid and the same amount of N-linked carbohydrates as C2. However, sgp 120 also contains O-linked carbohydrates. Monoclonal antibodies which specifically bind to sgp 120 were produced. One of these was produced from purified sgp 120 while the other was produced by immunization with purified C2. This latter monoclonal was found was found to be cross-reactive with sgp 120 during the process of subcloning of the original C2 antibody. During these studies a fast and efficient, high yield, method for the purification of C1 inhibitor, the major regulatory protein of the CCP and CAS, was developed.